Abstract
Background
The eThrombolysis in Cerebral Infarction (eTICI) score has been validated in proximal large artery occlusion (pLAOs). Despite the growing number of distal medium vessel occlusions (DMVOs) mechanical thrombectomies (MT) and the widespread utilization of the eTICI scoring system, its reliability and standardization for more distal occlusions have not been validated. We aim to evaluate the interrater reliability of eTICI scores in primary DMVOs.
Methods
This was a retrospective analysis of a prospectively maintained database for consecutive patients with pLAO and DMVO MT at a single comprehensive stroke center from 2015 to 2022. Two fellowship-trained neurointerventionalists blindly/independently assessed digital subtraction angiograms for final eTICI, followed by consensus reads for discrepancies.
Results
59 DMVO of 2248 thrombectomies [M3:29(50%)/M4:1(2%)/A1:3(5%)/A2:12(22%)/A3: 5(9%)/P1:7(12%)/P2:1(2%)] and 124 pLAOs of 308 thrombectomies [i-ICA:13(11%)/MCA-M1: 111(90%)] were included. The distribution of final eTICI scores was comparable between pLAO vs DMVOs (p = 0.82). The pLAO final eTICI score assessment between two readers demonstrated moderate reliability with a kappa0.77 (95%CI: 0.67–0.88), while the DMVO eTICI score assessment exhibited almost-perfect agreement with kappa 0.94 (95%CI: 0.90–0.99). The agreement between the consensus read and the original report in DMVOs was 0.86 (95% CI: 0.71–1.00) while for pLAO it was 0.83(95% CI: 0.76–0.90). The performance of eTICI was comparable amongst different DMVO territories as well as for distal vs. very distal occlusions.
Conclusion
eTICI score exhibited comparable performance for DMVO as compared to pLAO strokes. Further studies investigating DMVO eTICI grading and clinical outcomes are warranted.
Keywords: Stroke, thrombectomy, TICI scoring
Introduction
Mechanical thrombectomy (MT) has become the standard for the treatment of acute ischemic stroke (AIS) due to proximal large artery occlusion (pLAO) in the anterior and posterior circulations.1–9 An integral part of assessing the success of MT is the expanded Thrombolysis in Cerebral Infarction (eTICI) scoring system used to determine the extent of reperfusion. The eTICI score has been validated in pLAOs and is an independent predictor of clinical outcomes. 10
The evolution of stent retrievers and aspiration catheters has ushered in the next frontier of MT, allowing operators to effectively target primary distal medium vessel occlusions (DMVOs) involving middle cerebral artery (MCA) M3 segment, anterior cerebral artery (ACA), and posterior cerebral artery (PCA) occlusions. 11 Recent evidence suggest safety and potential efficacy of MT in these locations.12–13 Several trials are underway to better understand the clinical impact of MT in primary DMVOs considering that the anatomical, collateral status and technical aspects of pLAO cannot be directly extrapolated to DMVOs.
Despite the growing number of DMVO thrombectomies and the widespread utilization of the eTICI scoring system, its reliability and standardization for more distal occlusions has not been validated. We aim to evaluate the interrater reliability of eTICI scores in primary DMVOs.
Methods
Study design
This was a retrospective analysis of a prospectively maintained database for consecutive patients with proximal large artery occlusion (pLAO) and distal medium vessel occlusion (DMVO) ischemic strokes treated with MT at a single comprehensive stroke center.
Study cohort
pLAO strokes were defined as occlusions involving intracranial internal carotid artery (i-ICA) and middle cerebral artery (MCA) M1 segment spanning from November 2020 to December 2021. DMVOs encompassed MCA M3/M4, anterior cerebral artery (ACA) A1/A2/A3, and posterior cerebral artery (PCA) P1/P2 occlusions from January 2015 to December 2022. Inclusion criteria encompassed age >18 years, baseline eTICI 0–1, and digital subtraction angiography confirmation of occlusion site.
Imaging assessment
Two fellowship-trained neurointerventionalists independently assessed digital subtraction angiogram (DSA) runs blinded to clinical procedural characteristics, baseline occlusion site, in a random order (Reader 1 with two-year and reader 2 with nine-year experience). Each rater independently determined the final eTICI score blinded to clinical and radiological information. Baseline frontal and lateral digital subtraction angiography views were reviewed, followed by final frontal and lateral image review. A cineloop of the final lateral projection run was cycled for at least 2 runs, when reviewers were allowed to stop it for detailed inspection. A consensus read took place for discrepant reads.
Outcome measures
The primary endpoint was the comparison of agreement coefficients between Reader-1 vs Reader-2 eTICI for pLAO compared to DMVO. Secondary outcomes included the agreement coefficients between consensus read vs original procedural report eTICI scoring for pLAO compared to DMVO. Additionally, rates of parenchymal hematomas and SAH, as well as modified Rankin Score (mRS) 0–2 and mortality at 90 days were compared between the two groups.
Statistical analysis
Continuous variables are reported as median [Interquartile Range – IQR]. Categorical variables are reported as absolute and relative frequencies. Fleiss-Cohen's Weighted Kappa with quadratic weights was utilized. eTICI distributions were compared using Wilcoxon's rank sum test. eTICI performance within DMVOs was assessed in different territories (MCA M3/4 vs ACA vs PCA) and comparing distal and very distal (MCA M3, ACA A1, PCA P1 vs MCA M4, ACA A2/A3 PCA P2/P3). An alpha of 0.05 was considered. We used R Software v4.3.1 (R Foundation for Statistical Computing, Vienna, Austria) for all analyses. Sankey diagrams were generated using the ggsankey package.
Results
Patient characteristics
For the DMVO cohort, out of a total 2248 thrombectomies within the study period, 59 patients with a primary distal occlusion were included [M3:29(50%), M4:1(2%), A1: 3(5%), A2: 12(22%), A3: 5(9%), P1: 7 (12%), P2: 1(2%)]. For the pLAO group, 124 patients had a pLAO out of 308 patients within the specified study period [i-ICA:13(11%) and MCA-M1: 111(90%)].
There was no difference in age, sex, medical comorbidities and baseline mRS between the pLAO and DMVO cohorts. Patients with DMVO presented with lower NIHSS compared to the pLAO cohort. The DMVO cohort had higher baseline ASPECTS score and were more likely to receive intravenous thrombolysis. From a procedural standpoint, patients with DMVOs were more likely to undergo MT under general anesthesia compared to pLAO patients. All other baseline characteristics are reported on Supplemental Table 1. The distribution of final eTICI scores was comparable between pLAO vs DMVOs (p = 0.82; Table 1).
Table 1.
Final eTICI distributions between pLAO and DMVO occlusions.
| Characteristic | Distal, N = 59 1 | Proximal, N = 124 1 | p-value 2 |
|---|---|---|---|
| TICI (Consensus) | 0.986 | ||
| 0 | 5 (8.5%) | 0 (0.0%) | |
| 1 | 0 (0.0%) | 0 (0.0%) | |
| 2a | 3 (5.1%) | 0 (0.0%) | |
| 2b50 | 2 (3.4%) | 6 (4.8%) | |
| 2b67 | 6 (10.2%) | 19 (15.3%) | |
| 2c | 4 (6.8%) | 26 (21.0%) | |
| 3 | 39 (66.1%) | 73 (58.9%) |
n (%)
Wilcoxon rank sum test
Legend: eTICI, expanded Thrombolysis in Cerebral Infarction; pLAO, proximal Large Artery Occlusion; DMVO, Distal Medium Vessel Occlusion.
Interrater agreements of final eTICI scores pLAO and DMVO
The pLAO final eTICI score assessment between two readers demonstrated moderate reliability with a kappa value of 0.77 (95%CI: 0.67–0.88) (Supplemental Table 2), while the DMVO final eTICI score assessment exhibited almost perfect agreement with kappa value of 0.94 (95%CI: 0.90–0.99)(Supplemental Table 3). The variability in eTICI scores between Rater 1 and Rater 2 with proximal and distal occlusion sites is depicted in Figure 1. Additionally, the concordance between consensus read and the original report in DMVOs was 0.86 (95% CI: 0.71–1.00) (Supplemental Table 4) while similarly, the consensus read and the original report in pLAO was 0.83(95% CI: 0.76–0.90) (Supplemental Table 5).
Figure 1.
Sankey plot of eTICI evaluations by two raters. Legend: eTICI, expanded Thrombolysis in Cerebral Infarction.
Subgroup analyses/safety outcomes
The performance of eTICI was comparable amongst different DMVO territories as well as for distal and very distal occlusions (Supplemental Table 6). DMVO MT was associated with lower rates of parenchymal hematoma, while no difference in the rates of subarachnoid hemorrhage (SAH), 90-day mRS 0–2 or mortality between pLAO and DMVO cohorts were observed (Supplemental Table 7).
Discussion
The present study demonstrates comparable interrater reliability for DMVO and pLAO eTICI scoring, reinforcing the applicability of eTICI scoring for distal occlusions.
Effective reperfusion is essential for optimization of clinical outcomes. 10 The evolution of mechanical thrombectomy scoring systems for angiographic success initiated with the Arterial Occlusive Lesion (AOL) recanalization score followed by the Thrombolysis in Myocardial Infarction (TIMI) score (both derived from cardiology, being the latter focused on revascularization while the latter on tissue reperfusion). The Thrombolysis in Cerebral Infarction (TICI) was specifically applied for strokes, subsequently followed by the modified TICI (mTICI) and finally the eThrombolysis in Cerebral Infarction (eTICI) score. 14 The eTICI score provides a more detailed categorization of partial reperfusion and has been shown to strongly correlate with clinical outcomes. 10 Despite its widespread use, the reliability of the TICI score and its variations has limitations related to its interrater scoring variability. 15 Inter-rater reliability has been reported as moderate, and in the MR CLEAN Registry only 56% core lab adjudicated and operator mTICI scoring agreement was observed.16–18
MT has been increasingly performed for DMVO strokes.18–19 Recent evidence has suggested the safety and potential effectiveness of MT for distal vessel occlusion.12,20,21 The potential benefits of MT for distal vessel occlusions are being investigated by various randomized clinical trials, such as DUSK, ESCAPE MEVO, DISTAL and DISCOUNT.22–25 Although these trials are utilizing mTICI/eTICI, it is important to acknowledge that these scoring systems have been validated for pLAO. The application of eTICI to distal occlusions may present unique challenges due to the anatomical overlap of arterial territories, such as the anterior cerebral artery (ACA) and posterior cerebral artery (PCA), which complicates the delineation of the territory at risk. This complexity is further compounded by the variability of vascular territories, particularly MCA M3 s, and the smaller areas on DSA involved in distal occlusions. This is substantiated by data from the MR CLEAN Registry indicated that operators tended to overestimate M2/M3 occlusions as compared to more proximal occlusions. 18 The present study not only did not demonstrate lower agreement for DMVOs, but a higher inter-rater agreement coefficient for DMVO as compared to pLAO between the two blinded readers. Additionally, no significant differences were observed across different distal territories and distal vs very distal segments.
Our study has several limitations inherent to the single center design and retrospective nature. The sample size of distal occlusions is relatively small and 2/3 of the DMVO cases had final consensus eTICI 3 read, limiting not only the concordance assessment but also the power required to evaluate the correlation of the different degrees of DMVOs reperfusion scores and clinical outcomes. The study period for DMVO and pLAO differs, and although this should have no significant influence on the estimation of the primary outcome, it could have introduced bias in the analyses of hemorrhagic changes and clinical outcomes. The frequency of general anesthesia use was slightly (11%) different between the pLAO and DMVO groups which could have influenced the primary outcome, potentially explaining the enhanced agreement observed for the DMVO eTICI rating (κ = 0.94) compared to pLAO (κ = 0.77). Despite these limitations, our study provides valuable insights into the use of the extended Thrombolysis in Cerebral Infarction (eTICI) score for distal occlusions, paving the way for future research in this area.
eTICI score exhibited comparable performance for distal medium vessel occlusions DMVO as compared to pLAO strokes. Further studies investigating DMVO eTICI grading and clinical outcomes is warranted.
Supplemental Material
Supplemental material, sj-docx-1-ine-10.1177_15910199241262844 for Reliability assessment of distal occlusion eTICI scoring by Jaydevsinh N Dolia, Jonathan A Grossberg, Pedro N Martins, Mohamed A Tarek, Aqueel Pabaney, Alhamza R Al-Bayati, Raul G Nogueira and Diogo C Haussen in Interventional Neuroradiology
Acknowledgements
Dr Dolia participated in study conception, design of the work, interpretation of data and drafting of the article. Dr Martins and Tarek participated in study conception, design of the work, statistical analysis, interpretation of data. Dr Haussen supervised the entire project, contributed to methodology, design, statistical planning and manuscript writing. All authors contributed to data interpretation, composition and revision of the article. The manuscript was approved by all authors.
Footnotes
The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.
Funding: The authors received no financial support for the research, authorship, and/or publication of this article.
ORCID iDs: Jaydevsinh N. Dolia https://orcid.org/0000-0002-3924-047X
Jonathan A. Grossberg https://orcid.org/0000-0002-1152-8826
Alhamza R. Al-Bayati https://orcid.org/0000-0001-8103-1930
Supplemental material: Supplemental material for this article is available online.
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Supplementary Materials
Supplemental material, sj-docx-1-ine-10.1177_15910199241262844 for Reliability assessment of distal occlusion eTICI scoring by Jaydevsinh N Dolia, Jonathan A Grossberg, Pedro N Martins, Mohamed A Tarek, Aqueel Pabaney, Alhamza R Al-Bayati, Raul G Nogueira and Diogo C Haussen in Interventional Neuroradiology